We design and investigate a W15Ta15Cr35V35 (at.%) multicomponent alloy (MCA) with exceptional radiation resistance. The sintered WTaCrV alloy exhibits a body-centered cubic (BCC) matrix with dispersed coherent ordered nanoprecipitates. After ∼3-hour irradiation under 400 keV He+ at room temperature (RT) and 450°C with a fluence of 2 × 1017 ions/cm2, the irradiation hardening values of the MCA are about a quarter of those of pure tungsten counterparts irradiated at identical conditions. Besides, helium bubbles generated in the irradiated matrix of the MCA are much smaller, compared with those in the pure tungsten and other tungsten-rich alloys previously reported. The exceptional radiation resistance of the present WTaCrV alloy can be mainly attributed to two synergistic mechanisms. First, the high lattice distortion of the solid solution matrix promotes the local non-directional diffusion of irradiation defects, effectively suppressing the aggregation of irradiation defects and helium atoms along specific orientations. This facilitates more uniform nucleation of helium bubbles in the alloy matrix. Second, carbon was introduced during fast hot pressing sintering as interstitial solute to form carbon-rich coherent ordered nanoprecipitates. The carbon-vacancy complexes generated in the nanoprecipitates inhibit the nucleation and aggregation of helium atoms at the vacancies during He+ irradiation. The above two mechanisms synergistically enhance the resistance against He+ irradiation. This work thus demonstrates a design strategy for high radiation resistance alloys by introducing well-tuned ordered coherent nanoprecipitates in multicomponent alloy systems.